The Danish OCD and Tic Study (DOTS) is an NIH-funded genetic and epidemiological study of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) across Denmark. We aim to discover genetic and environmental factors that presumably interact to cause OCD and TS. To accomplish this we will genotype over 6,000 OCD cases and 4,000 TS cases and link these genotype data to registers with a wide array of health information. Key colleagues are located across Denmark.
OCD and TS are related and highly comorbid neurodevelopmental disorders. Their etiologies are unknown, but likely involve a complex interplay of partially overlapping genetic and environmental risk factors. Both are heritable (~50-60%), have high recurrence risks in first-degree relatives and co-occur in families. The goal of this study is to identify shared risk factors for TS and OCD as a window into their pathophysiology. .
We propose to markedly increase the currently-available sample sizes for TS and OCD GWAS by capitalizing on unique Danish resources. The Danish Neonatal Screening Biobank (DNSB) contains frozen blood spots from nearly all >2.1M Danes born after 1981 and is linked to medical registry data from the entire national health care system. These resources create an ideal opportunity to rapidly access DNA from large numbers of cases and population-based controls. Furthermore, a wealth of longitudinal medical registry data available provides an extraordinary opportunity to identify gene by environment interactions. In this study, we will first discover genomic loci associated with TS and OCD through a GWAS of over 6,000 OCD cases and 4,000 TS cases, along with 25,000 controls. Second, we will identify shared genetic risk factors for OCD and TS and their major comorbidities using modern statistical methods. Third, we will examine gene x environment interactions using GWAS and longitudinal epidemiological data. This will be accomplished by testing for interactions between polygenic risk scores and a range of epidemiological (paternal age, maternal and child infections, obstetric complications, infant health status, early life adversity, socioeconomic status) and genetic epidemiological (family history, co-aggregation of TS and OCD) variables.
OCD and TS cause significant disability profound personal and societal costs. We currently have a poor understanding of their etiology, limiting the development of novel therapeutic strategies. Successful completion of this proposal is expected to identify shared genetic and environmental risk factors for TS and OCD, providing a critical first step toward a detailed understanding of their pathophysiology.
Nissen J, Powell S, Koch SV, Crowley JJ, Matthiesen M, Grice DE, Thomsen PH, Parner E. Diagnostic validity of early-onset obsessive-compulsive disorder in the Danish Psychiatric Central Register: findings from a cohort sample. BMJ Open. 2017 Sep 18;7(9):e017172. https://bmjopen.bmj.com/content/7/9/e017172.long